P1642: OUTCOMES IN HOSPITALIZED PATIENTS WITH COMPLEMENT MEDIATED THROMBOTIC MICROANGIOPATHY
Authors: C. Logothetis, K. Finley, S. Huang, A. Wood, D. Laber, J. Eatrides
Journal: HemaSphere (2022)

Background: Complement-mediated (CM) thrombotic microangiopathy (TMA), also known as atypical hemolytic uremic syndrome is a serious and potentially life-threatening disorder characterized by dysregulation of the complement immune system. The advent of anti-C5 monoclonal antibodies (C5-mab) revolutionized the treatment of aHUS greatly reducing the morbidity and mortality. Experience outside clinical trials has been limited due to the rarity of the condition. Aims: The aim of this study was to examine the outcomes of hospitalized patients diagnosed with CM-TMA. All patients received C5-mab at our institution, hence, we aim to assess the safety, efficacy and toxicity of therapy. Methods: This was a retrospective study. The inclusion criteria comprised of diagnosis of CM-TMA (laboratory values consistent with TMA syndrome or TMA on a biopsy, with normal ADAMTS13 and absent shiga toxin). We used the following definitions through our data collection and analysis to assess treatment efficacy. Platelet response (PR): an increase in platelet count (PC) from baseline. Hematologic response (HR): PC and LDH normalization for at least 4 weeks. Complete TMA Response (CR): HR plus a decrease in Cr by 25% for at least 4 weeks without renal replacement therapy. Results: Thirty-four patients with CM-TMA received C5-mab (eculizumab and/or ravulizumab) at our institution between 2013-2021. The median age at diagnosis was 51 years. Twenty-seven (79%) patients were white, 6 (18%) were African American and (3%) were Asian. Presenting symptoms included fever in 4 (12%), neurologic deficit (weakness, fatigue, and altered mental status) in 14 (41%) and anasarca in 6 (18%). Renal replacement therapy was initiated in 20 (58.8%) subjects while receiving C5-mab. Six (18%) patients had kidney transplants prior to the diagnosis of CM-TMA and 4 (12%) patients required renal transplant after receiving C5-mab. Median (range) laboratory values prior to C5-mab demonstrated: PC 59/uL (8-308), LDH 890 U/L (420-4053), Cr 3.9 mg/dL (0.5-12.9) and Hemoglobin 7.1 g/dL (4.6-11.7). Therapy: Initiation of C5-mab occurred at a median of 11 (0-379) days after the initial TMA event. Outcomes: All patients responded: PR 30 (88%) and CR 4 (12%). Time to PR and CR in days were 9 (0-268) and 57.5 (29-120), respectively. Adverse events while on C5-mab were infections (medical equipment, pneumonia, and abscess) in 10 (29%) and headache in 2 (6%) individuals. Three (9%) patients died during their hospitalization. The causes of death were multi-organ failure from lupus flare, acute hypoxic respiratory failure from pulmonary hypertension and septic shock in a subject who had a severe E. faecium bacteremia prior to initiating C5-mab. Image:Summary/Conclusion: This is one of the largest real-world studies of hospitalized patients with CM-TMA treated with C5-mab. Limitations to this study include the retrospective nature and sample size, but the inclusion of all consecutive patients limited selection bias. We acknowledge that some hospitalized individuals with CM-TMA might not be diagnosed due to confounding illnesses. Since the diagnosis of CM-TMA usually takes several days to make, we speculate that patients with rapidly deteriorating organ function or with early demise might not reach diagnosis and therapy. Our findings confirm the efficacy of C5-mab at treating CM-TMA. We believe early diagnosis and initiation of therapy might avoid adverse outcomes. Large, long-term and prospective studies evaluating diagnostic criteria, therapy and outcomes in CM-TMA are warranted.